1. Field of the Invention
This invention is directed to a biocompatible composition of material to supply artificial parts for overcoming defects in the human body, and for osseous repair.
2. Description of the Prior Art
At present, the most effective ameliorative treatment for osseous repair is autogenous bone grafting, involving the transplantation of bone from another part of a patient's skeleton to the treatment site. Although widely employed, this method has several disadvantages including limited tissue availability and donor site morbidity. Donor site problems in particular discourage wider use of autogenous bone material in elective procedures (e.g., cosmetic bone augmentation, dental implants, periodontal therapy) where the risks to often outweigh potential benefits.
To overcome such problems both allogenic and alloplastic alternatives have been employed. Allogenic (freeze-dried) bone has been utilized with some success, but is expensive and does not heal as well as autogenous bone. Alloplastic ceramics, most notably the calcium phosphates (hydroxylapatite, tricalcium phosphate), have been used quite extensively in bone repair. Employed in both porous and nonporous forms, hydroxylapatite is quite stable in vivo and for all practical purposes, does not resorb. Tricalcium phosphate, while less stable in vivo, still undergoes bioresorption at a very slow rate. While quite appropriate for certain applications (e.g., onlay contouring), this extreme biostability translates into poor working qualities and inhibition of desired bony replacement in other commonly encountered situations.
Attempts to enhance both working qualities and bony replacement in calcium phosphate implants are represented by incorporation of calcium phosphate granules into a binding matrix such as plaster of Paris or collagen. While these adaptations certainly increase workability and encourage bony ingrowth through partial resorption, the phosphate particles will continue to endure and become incorporated in, rather than be replaced by, new host bone. By nature, this introduces planes of weakness into the bony structure which, while acceptable in certain situations, is undesirable in others, and would be preferably avoided where neuromuscular control of bone resorption is not an overriding concern (i.e., onlay contouring). Additional disadvantages include inability of the malleable collagen matrix to attain a solid state in vivo and the resistance of solidifying plaster matrices to molding, as well as the inability of either to be affixed by screw plate attachments.
Recently, the potential to identify and produce sufficient quantities of bone inductive agents has come closer to realization. Concurrently, the concept of delivering osteoprogenitor (pre-bone) cells from either autogenous or recombined sources to desired bone repair sites has developed into a potential repair adjunct. With the development of such biotechnology, hastened bony ingrowth into implants may significantly reduce, if not eliminate the need for composite inclusion of non-resorbable components such as calcium phosphate ceramic.
To this end, the literature has shown the ability of collagen, impregnated with a bone-derived inductive factor, to be transformed into a bony ossicle (complete with marrow cavity) when implanted in vivo, even in sites (such as muscle) where bone would not normally develop. In no case has this same protein been shown to promote bone formation in the absence of an appropriate scaffolding.
Stronger bioresorbable materials, such as ALCAP and polyHEMA are disadvantaged as potential delivery agents for delicate inductive biochemicals because of limitations in workability and the extreme conditions required for their fabrication. Tricalcium phosphate has recently been employed as an experimental delivery agent and found to resorb too slowly to be effective. Even in situations where introduction of inductive agents would not be desired, the necessity of application in precast or granular form still limits utility.
Calcium sulfate hemihydrate (CaSO.sub.4.5H.sub.2 O) is the dehydrated form of gypsum (CaSO.sub.4 H.sub.2 O). It is commonly supplied in powered form of various grades, usually differentiated by dehydration process, purity, and crystal morphology (alpha or beta). Used alone, it is rehydrated into plasters of various densities as determined by the amount of water added over an effective range (density increases with increase in plaster/water ratio; minimum water addition, depending on grade, approximately 20 ml/100 g).
More commonly available as dental plaster, the material is used in a variety of basic and "improved" (more finely and regularly crystallized and combined with mechanical enhancers such as calcium chloride) forms for applications ranging from fabrication of study or prosthetic casts to bite registrations. It is quite similar to plasters used in the building trade.
Collagen is the term applied to a family of fibrous proteins present in all multicellular organisms, subclassified into "Types" (I, II, III, etc.) based upon chemical and functional variations. In its natural state, it is the major fibrous element of skin, tendon, cartilage, blood vessels, and teeth. It is also 95% of the organic content of the bone (bone being 65% mineral and 35% organic) and is simply the most abundant protein in the body.
As a biomaterial, collagen is most frequently available as a reconstituted extract of bovine dermal collagen, although other sources have been used. By various chemical processes, the material is purified and reproduced in a variety of physical forms-sheets, tubes, sponges, powder, fibers, etc.--depending upon the application.
Therefore, the need exists for a rate-variable bioresorbable material which in addition to being easily combinable with advancing biotechnology possesses the inherent mechanical strength to be applied in stress-bearing situations, including an ability to accept plating screws. This material should be capable of resorption as quickly as 3 to 6 weeks if necessary. Additionally, this material should be versatile enough to be introduced as either a liquid, semi-solid or solid; injectable, moldable or pre-cast, while retaining its ability to achieve an acceptable threshold of mechanical strength ex situ or in situ. Such a material would not only reduce the need for use of alloplasts as bone substitutes, but also provide a more workable, utility vehicle in which to deliver them where still required.
Numbered among the many fallen contenders for the position of "more ideal bone substitute" are calcium sulfate and fibrillar collagen, individually. Calcium sulfate has been popular among Orthopedic Surgeons for many years as a biocompatible, quickly resorbable defect filler. Fibrillar collagen has gained some attention as a potential bone substitute recently, coincident to improvements in reconstitution and purification techniques, mainly as an alloplast and biosubstance delivery vehicle.
The alloplastic material with the most potential for meeting those requirements has been Hydroxylapatite (HA), alone or in combination with collagen, plaster or polymer. Synthetic HA [Ca.sub.10 (PO4).sub.6 (OH).sub.2 ] is chemically quite similar to the naturally occurring bone HA. It is quite strong, extremely biocompatible and is capable of direct bonding to bone. As a result, HA has become an unqualified commercial success.
But like autologous bone, HA has its deficiencies as well, most notably they are: 1) non-resorbability, and 2) inconvenient handling properties. HA does not actually integrate with bone and hence cannot replace its mechanical properties. Additionally, HA is sometimes associated with dehiscence, extrusion and/or migration of particles. And while recent developments in HA composite technology have diminished some of its shortcomings, it is clear that the ideal bone graft substitute has yet to be found.